One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice.

OBJECTIVES: To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men. DESIGN, PATIENTS, MEASUREMENTS: Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort. RESULTS: Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone (FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (p = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values. CONCLUSIONS: Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.

Spontaneous erectile function recovery among young men with erectile dysfunction taking tadalafil 5 mg once a day.

BACKGROUND: Daily (once a day [OaD]) tadalafil intake is a valuable option for men favoring spontaneous over scheduled sexual intercourse. AIM: The study sought to assess the rate of and the clinical factors associated with spontaneous, medication-free erectile function (EF) recovery after discontinuation of tadalafil 5 mg OaD in a cohort of young men seeking first medical help for psychogenic erectile dysfunction (ED) as their primary complaint. METHODS: Data from 96 consecutive patients <50 years of age seeking first medical help for ED and prescribed tadalafil 5 mg OaD were analyzed. Patients completed the International Index of Erectile Function (IIEF) and underwent baseline penile color Doppler ultrasound. Follow-up involved clinical assessments or phone interviews. Spontaneous medication-free EF recovery was defined as IIEF EF domain score >22 after tadalafil discontinuation, prompting cessation of follow-up. Descriptive statistics compared tadalafil OaD responders and nonresponders. Cox regression hazard models explored the association between baseline characteristics and EF recovery risk post-drug discontinuation. Kaplan-Meier analyses estimated EF recovery probability over time. OUTCOMES: The primary outcome was EF recovery after discontinuation of tadalafil 5 mg OaD. RESULTS: Overall, median age was 39 (interquartile range [IQR], 32-45) years. Of all, 82 (85.4%) patients achieved EF recovery after tadalafil OaD discontinuation, while 14 (14.6%) patients were identified as nonresponders. Median tadalafil usage time (from beginning to discontinuation) was 3 (IQR, 2-11) months. The most common treatment-emergent adverse event was headache in 9 (9.4%) patients. Nonresponders were older (43 [IQR, 42-45] years vs 38 [IQR, 31-44] years; P = .03), had higher body mass index (25.5 [IQR, 23.4-29.9] kg/m2 vs 23.6 [IQR, 21.8-25.9] kg/m2; P = .04), and reported lower baseline IIEF EF domain scores (12 [IQR, 7-15] vs 15 [IQR, 10-22]; P = .02) than responders. Nonresponders and responders did not differ in terms of baseline ED severity, Charlson comorbidity index, smoking, alcohol consumption, regular physical exercise, and color Doppler ultrasound parameters. Upon Cox regression analysis, younger age (hazard ratio, 0.95; 95% confidence interval, 0.92-0.99; P = .01) was associated to EF recovery, after adjusting for baseline ED severity, body mass index, smoking, and Charlson comorbidity index ≥1. The Kaplan-Meier analysis displays the probability of EF recovery over time, indicating rates of 43%, 60%, and 72% at 3-, 6-, and 12-month follow-up intervals, respectively. CLINICAL IMPLICATIONS: Tadalafil 5 mg OaD is an effective short-term treatment for psychogenic ED, allowing its discontinuation after achieving a normal medication-free EF. STRENGTHS AND LIMITATIONS: The main limitations are the limited number of participants and the potential neglect of confounding factors. CONCLUSION: Almost 1 out of 2 young men with primary psychogenic ED who were prescribed with tadalafil 5 mg OaD recovered spontaneous medication-free EF after 3 months of treatment. Overall, the younger the patient was, the higher the chance there was of spontaneous EF recovery after drug discontinuation.

Anti-Müllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia-findings from a multi-centric cross-sectional study.

STUDY QUESTION: Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular sperm extraction (mTESE)? SUMMARY ANSWER: A higher likelihood of +SR during mTESE is observed in men with iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, with good predictive accuracy achieved using an AMH threshold of <4 ng/ml. WHAT IS KNOWN ALREADY: AMH has been previously linked to +SR in men with iNOA undergoing mTESE prior to ART. STUDY DESIGN, SIZE, DURATION: A multi-centre cross-sectional study was carried out with a cohort of 117 men with iNOA undergoing mTESE at three tertiary-referral centres. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 117 consecutive white-European men with iNOA presenting for primary couple's infertility associated with a pure male factor at three centres were analysed. Descriptive statistics was applied to compare patients with negative (-SR) versus +SR at mTESE. Multivariate logistic regression models were fitted to predict +SR at mTESE, after adjusting for possible confounders. Diagnostic accuracy of the factors associated with +SR was assessed. Decision curve analyses were used to display the clinical benefit. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 60 (51.3%) men had an -SR and 57 (48.7%) had a +SR at mTESE. Patients with +SR had lower levels of baseline AMH (P = 0.005) and higher levels of estradiol (E2) (P = 0.01). At multivariate logistic regression analysis, lower levels of AMH (odds ratio: 0.79; 95% CI: 0.64-0.93, P = 0.03) were associated with +SR at mTESE, after adjusting for possible confounders (e.g. age, mean testicular volume, FSH, and E2). A threshold of AMH <4 ng/ml achieved the highest accuracy for +SR at mTESE, with an AUC of 70.3% (95% CI: 59.8-80.7). Decision curve analysis displayed the net clinical benefit of using an AMH <4 ng/ml threshold. LIMITATIONS, REASONS FOR CAUTION: There is a need for external validation in even larger cohorts, across different centres and ethnicities. Systematic reviews and meta-analysis to provide high level of evidence are lacking in the context of AMH and SR rates in men with iNOA. WIDER IMPLICATIONS OF THE FINDINGS: Current findings suggest that slightly more than one in two men with iNOA had -SR at mTESE. Overall, men with iNOA with lower levels of AMH had a significantly higher percentage of successful SR at surgery. A threshold of <4 ng/ml for circulating AMH ensured satisfactory sensitivity, specificity, and positive predictive values in the context of +SR at mTESE. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by voluntary donations from the Urological Research Institute (URI). All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

The Importance of Discordant Follicle Stimulating Hormone and Inhibin B Levels in Primary Infertile Men: Findings from a Cross-Sectional Study.

PURPOSE: We aimed to investigate the relationship between follicle stimulating hormone (FSH) and inhibin B (InhB). MATERIALS AND METHODS: Data from 1,230 consecutive men presenting for primary couple's infertility were analyzed. Health-significant comorbidities were scored with Charlson comorbidity index. Quartiles of FSH and InhB were considered to determine threshold values. Descriptive statistics and logistic regression models tested association between FSH and InhB values. RESULTS: Overall, 1,080 (87.8%) men had concordant FSH and InhB values. Conversely, 150 patients (12.2%) had discrepancies in FSH and InhB, with 78 (6.3%) and 72 (5.9%) men reporting both low and high FSH and InhB values, respectively. Infertile men with discordant values were younger (median [interquartile range] 38.0 years [34-41 years] vs. 36.0 years [31-40 years]); had smaller testicular volume (TV) (12 mL [10-15 mL] vs. 15 mL [12-20 mL]); and, had more frequently a sperm DNA fragmentation test >30% (179 [59.1%] vs. 40 [78.4%]) than those with concordant values (all p<0.05). Moreover, a higher frequency of previous cryptorchidism (27.3% vs. 11.9%), lower sperm concentration (3.0 million/mL [0.9-11.0 million/mL] vs. 13.8 million/mL [3.1-36.0 million/mL]), lower progressive sperm motility rates (12.0% [5.0%-25.3%] vs. 20.0% [7.0%-36.0%]), and greater rates of non-obstructive azoospermia (36.4% vs. 23.9%) were found in men with discordant FSH and InhB values (all p≤0.005). At multivariable logistic regression analysis, higher body mass index (odds ratio [OR], 1.08; p=0.001), smaller TV (OR, 0.91; p<0.001), and a history of cryptorchidism (OR, 2.49; p<0.001) were associated with discordant FSH and InhB values. CONCLUSIONS: More than one out of ten infertile men had discordant FSH and InhB values in the real-life setting showing worse clinical profiles than those with concordant levels. Smaller TV and history of cryptorchidism could be used as clinical markers to better tailor the need to test InhB.

Role of Follicle-stimulating Hormone, Inhibin B, and Anti-Müllerian Hormone in Predicting Sperm Retrieval from Men with Nonobstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: A Systematic Review and Meta-analysis.

Background and objective: No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE. Methods: We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis. Key findings and limitations: Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and -SR groups, with lower FSH (SMD -0.30), higher InhB (SMD 0.54), and lower AMH (SMD -0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00-1.06) or InhB (OR 1.01, 95% CI 1.00-1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73-0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend. Conclusions and clinical implications: Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE. Patient summary: We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.